BACKGROUND: Appendiceal tumors are rare and often unexpectedly discovered
in an acute situation, in which decision-making is difficult. To help
define the most appropriate management, a retrospective analysis was
undertaken to describe the clinicopathologic behavior of appendiceal
tumors, and the literature was reviewed of the management of the different
types of appendiceal tumors.

METHOD: From a single center, a histopathologic database of 7,970 appendectomies,
all appendiceal tumors, were identified and case notes reviewed. Analysis
of clinical presentation, histopathology, operation, and outcome is
presented.

RESULTS: During a 16-year period (7,970 appendectomies), 74 patients
(0.9 percent) with appendiceal tumors were identified: 42 carcinoid,
12 benign, and 20 malignant. Acute appendicitis was the most common
presentation (49 percent), and 9.5 percent were incidental findings.
Primary malignant tumors of the appendix were found in 0.1 percent of
all appendectomies. Secondary malignant disease was identified in the
appendix of 11 patients, most commonly (55 percent) from patients with
primary colorectal disease. There was a high incidence of synchronous
and metachronous colorectal cancer in all appendiceal tumors: carcinoids,
10 percent; benign tumors, 33 percent; secondary malignancies, 55 percent;
primary malignancies, 89 percent.

CONCLUSION: Appendiceal tumors are uncommon and most often present
as appendicitis. Most are benign and can be managed by appendectomy,
except adenocarcinomas and carcinoids larger than 2 cm, which are most
appropriately managed by right hemicolectomy. A suggested management
algorithm is provided. Controversy exists over the management of carcinoids
1 to 2 cm in size and adenocarcinoids. All types of appendiceal tumors
have a high incidence of synchronous and metachronous colorectal cancer.

Adenocarcinoma of the vermiform appendix. A population study.

Nielsen GP, Isaksson HJ, Finnbogason H, Gunnlaugsson GH.

Department of Pathology, University of Iceland, Reykjavik.

APMIS 1991 Jul;99(7):653-6 Abstract quote

We report seven cases of adenocarcinoma of the vermiform appendix occurring
in Iceland during 1974-1989.

The patients ranged in age from 25-83 years, mean age 55.1 years. There
were five males and two females. Five had mucinous adenocarcinoma, two
had adenocarcinoma. Four patients presented with symptoms and signs
of acute appendicitis and all had surgically resectable disease. Three
of these patients were alive with no evidence of disease four months,
two years and 15 years after presentation; one death of disease occurred
seven years after ileocecal resection. In three cases, the clinical
presentation was that of metastatic adenocarcinoma of unknown origin.
Of these patients two were diagnosed at autopsy and one after appendectomy
for perforated appendicitis. Survival in this group was six weeks, three
months and twelve months, respectively. In none of our patients was
the diagnosis made preoperatively and no tumors were found in appendices
removed incidental to other intra-abdominal operations.

The incidence of adenocarcinoma of the vermiform appendix in Iceland
during 1974-1989 was approximately 0.2 cases/100.000/year.

Context.-Carcinomas of the appendix are usually well-differentiated
mucinous adenocarcinomas that tend to produce pseudomyxoma peritonei
and do not show metastatic spread until late in the disease process.
In contrast, adenocarcinomas of the colon and rectum rarely result in
pseudomyxoma peritonei and frequently metastasize, even if mucinous
and well differentiated. These differences in behavior may be reflected
by differences at the molecular level.

Objectives.-To examine adenocarcinomas and their precursor lesions
(adenomas) of the appendix and colorectum and to determine whether differences
exist in the numbers of proliferating and apoptotic cells or in expression
of p53, bcl-2, and the standard form of CD44 (CD44s).

Design.-Retrospective analysis of surgical specimens.

Setting.-Multicenter study.

Patients.-Individuals treated surgically for tumors of the appendix
or colorectum.

Interventions.-Sections were cut from formalin-fixed surgical specimens
and immunohistochemical tests were performed for Ki-67 (as a marker
of proliferating cells), M30 (as a marker of apoptotic cells), p53,
CD44s, and bcl-2. Main Outcome Measures.-Expression of Ki-67, M30, p53,
CD44s, and bcl-2 in tumor cells. Results.-The appendiceal adenomas showed
significantly lower Ki-67 counts, p53 expression, and bcl-2 expression.
When compared with adenocarcinomas of the colorectum in general (mucinous
and nonmucinous), the appendiceal adenocarcinomas showed significantly
lower Ki-67 counts, M30 counts, and CD44s expression. However, when
the analysis was confined to well-differentiated mucinous adenocarcinomas,
only the M30 count was significantly different.

Conclusions.-The lower proliferative and apoptotic activity of appendiceal
carcinomas and the lower CD44s expression are in keeping with their
more indolent behavior compared with adenocarcinomas of the colorectum.
However, when only the subset of well-differentiated mucinous adenocarcinomas
was compared, only the apoptotic activity was different, suggesting
that the other differences were related to the morphologic structure
of the lesions.

CHROMOSOMAL ABNORMALITIES

Mucinous and nonmucinous appendiceal adenocarcinomas: different clinicopathological
features but similar genetic alterations.

Our findings suggest that mucinous and nonmucinous carcinomas of appendix
have similar genetic alterations, but different clinical presentation
and prognosis.

GROSS APPEARANCE/
CLINICAL VARIANTS

CHARACTERIZATION

GENERAL

Primary epithelial tumors of the appendix and a reappraisal of the appendiceal
"mucocele".

Aranha GV, Reyes CV.

Dis Colon Rectum 1979 Oct;22(7):472-6 Abstract quote

A 28-year review of the records at Hines V.A. Medical Center revealed
17 primary epithelial tumors of the appendix. Five of these tumors were
benign and 12 malignant. It is suggested that the term mucocele be abandoned,
because it represents the end result rather than a definite pathologic
entity.

The majority of benign tumors and carcinoid tumors of the appendix
are discovered incidentally to other procedures. The majority of adenocarcinomas
cause symptoms and signs of appendicitis. Simple appendectomy is sufficient
treatment of all benign tumors of the appendix, and for all carcinoids
that show no gross local metastases and are less than 2 cm in diameter.
Simple appendectomy followed by right hemicolectomy or initial right
hemicolectomy is the treatment of choice for all carcinoids of the appendix
that show gross local metastases and are 2 cm or more in diameter and
for all adenocarcinomas of the appendix, whether mucinous or colonic,
in the absence of distant metastasis.

A new classification for primary epithelial tumors of the appendix
is suggested.

Primary appendiceal adenocarcinoma.

Ozakyol AH, Saricam T, Kabukcuoglu S, Caga T, Erenoglu E.

Division of Gastroenterology, School of Medicine, Osmangazi University,
Eskisehir, Turkey.

Am J Clin Oncol 1999 Oct;22(5):458-9 Abstract quote

Adenocarcinoma of the appendix is rarely encountered and is usually
discovered at the pathology examination of the surgical specimen. Adenocarcinoma
of the vermiform appendix is a rare neoplasm and constitutes <0.5%
of all gastrointestinal neoplasms.

There is no symptom of appendiceal cancer, and it is very difficult
to diagnose preoperatively. Most female patients are diagnosed as having
a gynecologic disease. Second primary synchronous and metachronous neoplasms,
especially in the gastrointestinal tract, are found in up to 35% of
patients with appendix adenocarcinoma.

We report a case of adenocarcinoma in a 56-year-old woman misdiagnosed
as having right ovarian carcinoma, and we review the literature.

VARIANTS

OVARIAN METASTASIS

The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas:
a clinicopathologic and immunohistochemical analysis of tumors often
misinterpreted as primary ovarian tumors or metastatic tumors from other
gastrointestinal sites.

Ronnett BM, Kurman RJ, Shmookler BM, Sugarbaker PH, Young RH.

Department of Pathology, The Johns Hopkins School of Medicine, Baltimore,
Maryland, USA

The most common presentation was a pelvic mass. The appendiceal and
ovarian tumors were diagnosed concurrently in 15 cases; in the remaining
five, the ovarian tumors were diagnosed before the appendiceal tumor.
The appendiceal adenocarcinomas demonstrated four morphologic patterns:
1) signet ring cell type, with or without glandular or goblet cell differentiation
(14 cases); 2) mixed signet ring cell and intestinal type (two cases);
3) intestinal type (two cases); and 4) typical colorectal type (two
cases).

The ovarian tumors were bilateral in 16 cases and were histologically
similar to the associated appendiceal tumor in each case. Ovarian metastases
that demonstrate signet ring cell, glandular, and goblet cell differentiation
mimic metastases from gastric adenocarcinoma. Those that are derived
from well-differentiated mucinous appendiceal adenocarcinomas mimic
primary ovarian mucinous tumors and metastases from the pancreas and
biliary tract. Metastases of appendiceal adenocarcinomas of colorectal
type simulate both metastatic colorectal carcinoma and primary ovarian
endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically
identical in each case.

Approximately 50% of the appendiceal and ovarian tumors were positive
for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK
20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal
origin; CK 7 positivity does not confirm ovarian origin, because appendiceal
carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma
should be considered in the differential diagnosis of mucinous ovarian
tumors with signet ring cell, goblet cell, or intestinal type differentiation,
especially when these tumors are associated with extraovarian disease
and are bilateral.

Adenocarcinoma of the appendix is unusual at any age but occurs mostly
in an elderly population.

The authors report a unique case presenting in a 10-year-old child
and emphasize the importance of subjecting all resected specimens to
histological examination.

HISTOLOGICAL TYPES

CHARACTERIZATION

GENERAL

MUCINOUS

NON-MUCINOUS

VARIANTS

DIFFERENTIAL DIAGNOSIS

KEY DIFFERENTIATING FEATURES

ADENOCARCINOID

Adenocarcinoid (mucinous carcinoid) of the appendix.

Edmonds P, Merino MJ, LiVolsi VA, Duray PH.

Gastroenterology 1984 Feb;86(2):302-9 Abstract quote

Carcinoid tumors of the appendix are common incidental findings, but
appendiceal tumors with histologic features of both carcinoids and adenocarcinomas
are rare, and their biologic behavior is still unclear.

We studied 10 such cases among 45 appendiceal tumors seen at Yale-New
Haven Hospital between 1960 and 1982. The patients, ranging in age from
23 to 65 yr, were all clinically symptomatic [acute appendicitis (5);
abdominal mass (5)]. Right colectomy was performed in 5 patients; the
other 5 underwent appendectomy only. In 1 case, metastasis to a lymph
node was detected; 2 patients had ovarian metastases, and 4 patients
had cecal invasion. One of the 10 patients died of widely disseminated
tumor, 2 are living with persistent disease, and 5 remained free of
disease from 1 to 5 yr after initial surgery. Two cases were lost to
follow-up.

We conclude that the histology of these lesions is distinctive, enabling
their differentiation from ordinary carcinoids. Because these lesions
behave in a clinically more aggressive fashion than the usual appendiceal
carcinoids, but are less virulent than adenocarcinoma, we support their
classification as adenocarcinoids.

GOBLET CELL CARCINOID

Goblet cell carcinoid tumor of the appendix. Report of five cases and
review of the literature.

Chen V, Qizilbash AH.

Arch Pathol Lab Med 1979 Apr;103(4):180-2 Abstract quote

Five cases of goblet cell carcinoid tumor of the appendix showed characteristic
histologic features that justified classification of these lesions as
mucinous variants of carcinoid tumor. The tumor has low-grade malignancy,
and metastases are uncommon.

Resemblance to mucinous adenocarcinoma of the appendix is striking,
and the features that help to differentiate the two lesions are delineated.

Metastatic tumors to the appendix are not common. However, these tumors
should be one of the differential diagnoses in patients with known primary
malignancy, who present with signs and symptoms of acute appendicitis.

We report a case of an elderly male with poorly differentiated bronchogenic
adenocarcinoma which metastasized to the appendix.

PROGNOSIS AND TREATMENT

CHARACTERIZATION

PROGNOSTIC FACTORS

GENERAL

Primary adenocarcinoma of the appendix.

Delgado RR Jr, Mullen JT, Ehrlich FE.

South Med J 1975 Aug;68(8):976-8 Abstract quote

A case of primary adenocarcinoma of the appendix in which the patient
had the usual symptoms of acute appendicitis is presented. A review
of the literature showed the potential for early extension and nodal
metastasis in this lesion and led to the recommendation of right hemicolectomy
as the treatment of choice.

The operation should be done either primarily or secondarily after
an appendectomy and should lead to a five-year survival of approximately
45%. Every effort should be made to make the diagnosis and provide definitive
treatment at the primary operation by examining the appendix grossly
and obtaining frozen section microscopic study of any suspicious tumor
or ulceration.

Adenocarcinoma of the appendix: a clinicopathologic study.

Didolkar MS, Fanous N.

Dis Colon Rectum 1977 Mar;20(2):130-4 Abstract quote

Clinicopathologic correlation and survival were evaluated in 11 patients
with adenocarcinomas of the appendix. This extremely rare tumor was
seen most often in patients in the fifth decade of life. Acute appendicitis
was the most common mode of presentation (8/11). A few patients (3/11)
showed signs of distant metastases from an occult primary tumor in the
appendix.

Primary malignant neoplasms of the appendix.

McCusker ME, Cote TR, Clegg LX, Sobin LH.

Department of Epidemiology and Preventive Medicine, University of
Maryland, Baltimore, Maryland.

Cancer 2002 Jun 15;94(12):3307-12 Abstract quote

BACKGROUND
Cancer of the appendix is an uncommon disease that is rarely suspected
rarely before surgery. Although several case series of these tumors
have been published, little research has been anchored in population-based
data on cancer of the appendix.

METHODS
This analysis included all actively followed cases of appendiceal neoplasms
reported to the National Cancer Institute's Surveillance, Epidemiology
and End-Results (SEER) program between 1973 and 1998. Tumors were classified
as "colonic type" adenocarcinoma, mucinous adenocarcinoma,
signet ring cell carcinoma, goblet cell carcinoid, and "malignant
carcinoid" (SEER only collects data on carcinoids specifically
classified as malignant). We compared incidence, overall survival and
survival rates by extent of disease at diagnosis.

RESULTS
Between 1973 and 1998, 2117 appendiceal malignancies were reported to
the SEER program, of which 1645 cases were included in the analysis.
Age-adjusted incidence of cancer of the appendix was 0.12 cases per
1,000,000 people per year. Demographic characteristics of patients with
goblet cell carcinoid tumors were midway between those of patients with
malignant carcinoid and all types of adenocarcinomas. After controlling
for age and extent of disease at diagnosis, the overall survival rate
for patients diagnosed between 1983 and 1997 (n = 1061) was significantly
worse for those with signet ring cell carcinoma than for those with
any other tumor type (P < 0.01). In addition, overall survival rates
were better for patients with malignant carcinoid (P = 0.01).

CONCLUSIONS
Demographic characteristics of patients with cancer of the appendix
vary by histology. Except for signet ring cell carcinoma and malignant
carcinoid, the extent of disease at time of diagnosis is a more important
predictor of survival than histology.

TREATMENT

SURGERY

Adenocarcinoma of the vermiform appendix: retrospective study and literature
review.

Panton ON, Bell GA, Owen DA.

Can J Surg 1983 May;26(3):276-9 Abstract quote

Adenocarcinoma of the vermiform appendix is a rare clinical entity,
fewer than 200 cases having been reported.

The authors carried out a retrospective review over a 25-year period
and found five patients admitted to the Vancouver General Hospital with
primary appendiceal adenocarcinoma. Four other patients, initially reported
as having appendiceal adenocarcinoma, were found after critical microscopic
review to have had either benign disease or mucinous carcinoid. Primary
epithelial neoplasms of the appendix demonstrate a wide variety of histologic
types and because of the different clinical behaviour, an accurate diagnosis
must be made.

For the benign tumours, appendectomy alone will suffice but for adenocarcinoma
of the appendix, right hemicolectomy is recommended.

Adenocarcinoma of the appendix.

Ferro M, Anthony PP.

Dis Colon Rectum 1985 Jun;28(6):457-9 Abstract quote

Three cases of adenocarcinoma of the appendix are reported. All three
patients presented with acute appendicitis and the tumors were diagnosed
only on histologic examination of the excised appendix.

The first patient subsequently had a right hemicolectomy and was proven
to have a Dukes' B tumor. The second patient probably had a Dukes' B
also, but no further surgery was performed because of advanced presenile
dementia. Advanced disease was found in the third patient. Analysis
of 145 cases reported over the last ten years suggests that, unless
the tumor is in Dukes' A stage, right hemicolectomy should be carried
out if the patient is fit for radical surgery.

The overall prognosis appears to be the same as that for carcinoma
of the colon.

Adenocarcinoma of the vermiform appendix.

Harris GJ, Urdaneta LF, Mitros FA.

Department of Surgery, University of Iowa, College of Medicine,
Iowa City.

J Surg Oncol 1990 Aug;44(4):218-24 Abstract quote

Primary adenocarcinoma of the appendix is rare. Eleven patients with
this rare neoplasm have been evaluated at our institution over a 50-year
period.

We have reviewed the presentation and clinical course of these patients,
and have compared them with those described in the literature. The presenting
signs and symptoms, physical findings, and treatment were similar to
those described in the literature. However, the 5-year survival of 20%
is lower than most series, and reflects the advanced stage of disease
at the time of diagnosis in this group of patients.

The natural history of surgically treated primary adenocarcinoma
of the appendix.

Nitecki SS, Wolff BG, Schlinkert R, Sarr MG.

Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Ann Surg 1994 Jan;219(1):51-7 Abstract quote

OBJECTIVE: The aim of this investigation was to determine the prognostic
variables and optimal surgical procedure for patients with adenocarcinoma
of the appendix.

SUMMARY BACKGROUND DATA: Primary adenocarcinoma of the appendix is
a rare malignancy that constitutes less than 0.5% of all gastrointestinal
neoplasms. However, the prognostic factors and the preferred surgical
procedure and outcome are poorly understood.

METHODS: The authors reviewed their institutional experience from 1976
to 1992 in treating 94 consecutive patients with primary adenocarcinoma
of the appendix. Patients with carcinoid tumors or those in whom the
diagnosis of primary cecal cancer could not be ruled out were excluded
from the study.

RESULTS: Fifty-two (55%) patients had the mucinous variety, of which
22 had pseudomyxoma peritonei; the other 45% had the colonic and adenocarcinoid
types of tumor. The most common presentation was that of acute appendicitis.
Interestingly, in no patients was the correct diagnosis made before
surgery, and it was entertained intraoperatively in only 30 patients
(32%). The cure 5-year survival rate was 55%, but it varied with stage
(A, 100%; B, 67%; C, 50%; and D, 6%; p < 0.01) and with grade (I,
68%, and III, 7%; p < 0.01). Patients with the mucinous type had
a better prognosis than those with the colonic type (p < 0.01). The
survival rate was superior after right hemicolectomy versus appendectomy
alone (68% vs. 20%, p < 0.001). Right hemicolectomy performed as
a secondary procedure resulted in the upstaging of 38% of the patients'
tumors. A second primary malignancy occurred in 33 patients (35%), of
which 17 were located in the gastrointestinal tract.

CONCLUSIONS: Primary adenocarcinoma of the appendix should be treated
by right hemicolectomy, even if it is a secondary procedure. Surveillance
for synchronous or metachronous tumors, especially in the gastrointestinal
tract, is warranted.